An OECD TG 428 study ring trial with 14C-Caffeine demonstrating repeatability and robustness of the dermal absorption in vitro method

Kluxen, Felix M.; Totti, Styliani; Maas, Wilfred; Toner, Frank; Page, Leanne; Webbley, Kathryn; Nagane, Rajendra; Mingoia, Robert T.; Whitfield, Christine; Kendrick, John; Valentine, Claire; Dorange, Jeanne Bernal; Egron, Camille; Imart, Camille; Domoradzki, Jeanne; Fisher, P.; Lorez, Christine; McEuen, Steve; Felkers, Edgars; Chen, Tao; Wiemann, Christiane

doi:10.1016/j.yrtph.2022.105184

Cited by 3 publications

(1 citation statement)

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“…This may also interact with exposure duration, which may vary according to the OECD test guideline and should only be representative for the risk assessment, e.g., cover a typical workday exposure scenario of 6–10 hours. It was recently shown that the harmonization of study parameters leads to very compatible in vitro dermal absorption study outcomes independent of the performing laboratory (Kluxen et al 2022 ). Further, evaporation or drying of the test item can affect dermal absorption (Hewitt et al 2020 ).…”

Section: Discussionmentioning

confidence: 99%

A new conceptional model for deriving average dermal absorption estimates from studies with multiple tested concentrations for non-dietary risk assessment of pesticides

Kluxen¹,

Felkers²,

McEuen

et al. 2022

Arch Toxicol

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Dermal absorption values are used to translate external dermal exposure into potential systemic exposure for non-dietary risk assessment of pesticides. While the Environmental Protection Agency of the United States of America (US EPA) derives a common dermal absorption factor for active substances covering all related products, the European Food Safety Authority (EFSA) requests specific product-based estimates for individual concentrations covering the intended use rates. The latter poses challenges, because it disconnects exposure dose from applied dose in absorption studies, which may not be suitable in scenarios where concentration is not relevant. We analyzed the EFSA dermal absorption database, collected 33 human in vitro studies from CropLife Europe (CLE) companies, where ≥3 in-use dilution concentrations were tested, and 15 dermal absorption triple pack datasets. This shows that absolute dermal absorption correlates with absolute applied dose on a decadic logarithm-scale, which is concordant with the toxicological axiom that risk is driven by exposure dose. This method is radically different from the current European approach focused on concentrations and offers new insights into the relationship of internal and external exposure doses when utilizing data from in vitro studies. A single average dermal absorption value can be simply derived from studies with multiple tested concentrations, by calculating the y-intercept of a linear model on a decadic logarithm scale while assuming a slope of 1. This simplifies risk assessment and frees resources to explore exposure refinements. It also serves as a basis to harmonize dermal absorption estimation globally for use in exposure-driven risk assessments.

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Section: Discussionmentioning

confidence: 99%